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Gene Therapy Clinical Study in Adult PKU (pheNIX)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03952156
Recruitment Status : Recruiting
First Posted : May 16, 2019
Last Update Posted : March 2, 2020
Information provided by (Responsible Party):
Homology Medicines, Inc

Brief Summary:
This is a Phase 1/2, open-label, randomized, concurrently-controlled, dose escalation study to evaluate the safety and efficacy of HMI-102 in adult PKU subjects with PAH deficiency. Participants will receive a single administration of HMI-102 and will be followed for safety and efficacy for 1 year.

Condition or disease Intervention/treatment Phase
Phenylketonurias PAH Deficiency Genetic: HMI-102 Phase 1 Phase 2

Detailed Description:
This study will evaluate the safety and efficacy of HMI-102 gene therapy in adult subjects with PKU due to PAH deficiency. Subjects will receive a single dose of HMI-102 administered intravenously. Up to 3 dose levels of HMI-102 may be investigated in this study. At a given dose level, a minimum of 2 subjects will be enrolled and dosed. Dosing of the first two subjects will be staggered. Following evaluation of data from the first 2 subjects in a cohort, a decision can be made to either escalate to the next dose level or expand the cohort at the selected dose level. If the cohort is expanded, additional subjects will be randomized to receive HMI-102 or a concurrent delayed treatment control arm. Subjects in the delayed treatment control will be eligible to receive HMI-102 after 24 weeks.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open-Label, Randomized, Concurrently-Controlled, Dose Escalation Study to Evaluate the Safety and Efficacy of HMI-102 in Adult PKU Subjects With PAH Deficiency
Actual Study Start Date : June 10, 2019
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : September 2021

Arm Intervention/treatment
Experimental: Cohort 1
Dose Level 1 of HMI-102 delivered intravenously one time
Genetic: HMI-102
HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene

Experimental: Cohort 2
Dose Level 2 of HMI-102 delivered intravenously one time
Genetic: HMI-102
HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene

Experimental: Cohort 3
Dose Level 3 of HMI-102 delivered intravenously one time
Genetic: HMI-102
HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene

No Intervention: Delayed Treatment Control
Control subjects will generally have the same assessments as treated subjects. Control subjects will undergo pre-baseline procedures to confirm that they are eligible to receive treatment with HMI-102. Once eligible control subjects are dosed with HMI-102, they will initiate the same post-dose procedures as subjects who received HMI-102.

Primary Outcome Measures :
  1. Incidence and severity of treatment-emergent adverse events (TEAE) and serious TEAEs [ Time Frame: Baseline to Week 52 ]
    Subjects with at least one TEAE or serious TEAE

  2. Incidence of sustained plasma Phe concentration of ≤360 μmol/L at 24 weeks post dose [ Time Frame: Baseline to Week 24 ]
    Subjects achieving a sustained plasma Phe concentration ≤360 μmol/L at 24 weeks post dose

Secondary Outcome Measures :
  1. Plasma Phe Concentration [ Time Frame: Baseline to Week 52 ]
    Change in plasma Phe concentration at 24 weeks

  2. Incidence of achieving a plasma Phe concentration to ≤360 μmol/L [ Time Frame: Baseline to Week 52 ]
    Subjects achieving plasma Phe concentration ≤360 μmol/L at each time point during the study

Other Outcome Measures:
  1. Phenylketonuria Quality of Life Questionnaire (PKU-QOL) [ Time Frame: Baseline to Week 52 ]
    Change in PKU-QOL

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Key Inclusion Criteria:

  • Adults 18-55 years of age at the time of informed consent
  • Diagnosis of classic phenylketonuria (PKU) due to PAH deficiency
  • Two plasma Phe values with a concentration of ≥ 600 μmol/L drawn at least 48 hours apart during the screening period and at least one historical value ≥ 600 μmol/L in the preceding 12 month.
  • Subject has the ability and willingness to maintain their baseline diet, whether Phe-restricted or unrestricted, after administration of HMI-102, unless otherwise directed

Key Exclusion Criteria:

  • Subjects with PKU that is not due to PAH deficiency
  • Presence of anti-AAVHSC15 neutralizing antibody
  • ALT >1.5x ULN and AST >1.5x ULN
  • Alkaline phosphatase >1.5x ULN.
  • Total bilirubin >1.5x ULN, direct bilirubin ≥ 1.5x ULN
  • Serum creatinine >1.5x ULN
  • Hematology values outside of the normal range (hemoglobin <11.0 g/dL for males or <10.0 g/dL for females; white blood cells (WBC) <3,000/μL; absolute neutrophils <1500/μL; platelets <100,000/μL)
  • Hemoglobin A1c >7.9% or fasting glucose >200 mg/dL
  • Any clinically significant abnormal laboratory result at screening, in the opinion of the Investigator
  • Contraindication to corticosteroid use or conditions that could worsen in the presence of corticosteroids, as assessed and determined by the investigator

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03952156

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Contact: Steven Glyman, M.D. 781-819-0967

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United States, Georgia
Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30322
Contact: Eleanor Botha    404-778-8517   
United States, Illinois
Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Carolyn Ries    312-227-6004   
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Eorna Maguire    617-919-1399   
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Catherine Miller    212-659-1456   
United States, Ohio
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Mallory Rowell    614-722-2512   
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Bianca Ferreira    267-426-1368    FERREIRAB@EMAIL.CHOP.EDU   
UPMC Children's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Jennifer Baker    412-692-6378   
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84108
Contact: Carrie Bailey    801-587-3605   
Sponsors and Collaborators
Homology Medicines, Inc
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Responsible Party: Homology Medicines, Inc Identifier: NCT03952156    
Other Study ID Numbers: HMI-102-101
First Posted: May 16, 2019    Key Record Dates
Last Update Posted: March 2, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Homology Medicines, Inc:
PAH Deficiency
Adeno Associated Virus
Additional relevant MeSH terms:
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Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases